A Phase 2 Randomized Clinical Trial Evaluating 4-Dimensional Computed Tomography Ventilation-Based Functional Lung Avoidance Radiation Therapy for Non-Small Cell Lung Cancer.

PURPOSE: To determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiation therapy preserves pulmonary function compared with standard radiation therapy for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiation therapy with either stereotactic body radiation therapy or conventionally fractionated radiation therapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiation therapy or functional lung avoidance radiation therapy. The primary endpoint was the change in Jacobian-based ventilation as measured on 4DCT from baseline to 3 months postradiation. Secondary endpoints included changes in volume of high- and low-ventilating lung, pulmonary toxicity, and changes in pulmonary function tests (PFTs). RESULTS: A total of 122 patients were randomized and 116 were available for analysis. Median follow up was 29.9 months. Functional avoidance plans significantly (P < .05) reduced dose to high-functioning lung without compromising target coverage or organs at risk constraints. When analyzing all patients, there was no difference in the amount of lung showing a reduction in ventilation from baseline to 3 months between the 2 arms (1.91% vs 1.87%; P = .90). Overall grade ≥2 and grade ≥3 pulmonary toxicities for all patients were 24.1% and 8.6%, respectively. There was no significant difference in pulmonary toxicity or changes in PFTs between the 2 study arms. In the conventionally fractionated cohort, there was a lower rate of grade ≥2 pneumonitis (8.2% vs 32.3%; P = .049) and less of a decline in change in forced expiratory volume in 1 second (-3 vs -5; P = .042) and forced vital capacity (1.5 vs -6; P = .005) at 3 months, favoring the functional avoidance arm. CONCLUSIONS: There was no difference in posttreatment ventilation as measured by 4DCT between the arms. In the cohort of patients treated with conventionally fractionated radiation therapy with functional lung avoidance, there was reduced pulmonary toxicity, and less decline in PFTs suggesting a clinical benefit in patients with locally advanced NSCLC.

Characterization of mechanical and radiation isocenter on an MR-guided radiotherapy (MRgRT) Linac.

BACKGROUND AND PURPOSE: In the emerging paradigm of stereotactic radiosurgery being proposed for MR-guided radiotherapy (MRgRT), assessment of mechanical geometric accuracy is critical for the implementation of stereotactic delivery. We benchmarked the mechanical accuracy of an MR Linac system that lacks an onboard detector/array. Our mechanical tests utilize a half beam block (HBB) geometry that takes advantage of the sensitivity of a partially occluded detector. MATERIALS AND METHODS: Mechanical tests benchmarked the couch, MLC, and gantry geometric accuracy for an MR-Linac system. An HBB technique was used to irradiate an ionization chamber profiler (ICP) array with partial occlusion of individual detectors for characterization of MLC skew, beam divergence displacement, and RT isocenter localization. The sensitivity of the partially occluded detector's ICP-X (detector width) and ICP-Y (detector length) was characterized by displacing the detector relative to radiation isocenter by 0.2 mm increments, introduced through couch motion. The accuracy of the HBB ICP technique was verified with a starshot using radiochromic film, and the reproducibility was verified on a conventional C-arm Linac and compared to Winston-Lutz. RESULTS: The sensitivity of the HBB technique as quantified through the dose difference normalized to open field as a function of displacement from RT isocenter was 6.4%/mm and 13.0%/mm for the ICP-X and ICP-Y orientation, respectively, due to the oblong detector orientation. Couch positional accuracy and sag was within ±0.1 mm. Maximum MLC positional displacement was 0.7 mm with mean MLC skew at 0.07°. The maximum beam divergence displacement was 0.03 mm. The gantry angle was within 0.1°. Independent verification of the RT isocenter localization procedure produced repeatable results. CONCLUSION: This work serves for characterizing the mechanical and geometric radiation accuracy for the foundation of an MR-guided stereotactic radiosurgery program, as demonstrated with high sensitivity and independent validation.

Validation of CT-based ventilation and perfusion biomarkers with histopathology confirms radiation-induced pulmonary changes in a porcine model.

Imaging biomarkers can assess disease progression or prognoses and are valuable tools to help guide interventions. Particularly in lung imaging, biomarkers present an opportunity to extract regional information that is more robust to the patient's condition prior to intervention than current gold standard pulmonary function tests (PFTs). This regional aspect has particular use in functional avoidance radiation therapy (RT) in which treatment planning is optimized to avoid regions of high function with the goal of sparing functional lung and improving patient quality of life post-RT. To execute functional avoidance, detailed dose-response models need to be developed to identify regions which should be protected. Previous studies have begun to do this, but for these models to be clinically translated, they need to be validated. This work validates two metrics that encompass the main components of lung function (ventilation and perfusion) through post-mortem histopathology performed in a novel porcine model. With these methods validated, we can use them to study the nuanced radiation-induced changes in lung function and develop more advanced models.

Quantifying robustness of CT-ventilation biomarkers to image noise.

Purpose: To quantify the impact of image noise on CT-based lung ventilation biomarkers calculated using Jacobian determinant techniques. Methods: Five mechanically ventilated swine were imaged on a multi-row CT scanner with acquisition parameters of 120 kVp and 0.6 mm slice thickness in static and 4-dimensional CT (4DCT) modes with respective pitches of 1 and 0.09. A range of tube current time product (mAs) values were used to vary image dose. On two dates, subjects received two 4DCTs: one with 10 mAs/rotation (low-dose, high-noise) and one with CT simulation standard of care 100 mAs/rotation (high-dose, low-noise). Additionally, 10 intermediate noise level breath-hold (BHCT) scans were acquired with inspiratory and expiratory lung volumes. Images were reconstructed with and without iterative reconstruction (IR) using 1 mm slice thickness. The Jacobian determinant of an estimated transformation from a B-spline deformable image registration was used to create CT-ventilation biomarkers estimating lung tissue expansion. 24 CT-ventilation maps were generated per subject per scan date: four 4DCT ventilation maps (two noise levels each with and without IR) and 20 BHCT ventilation maps (10 noise levels each with and without IR). Biomarkers derived from reduced dose scans were registered to the reference full dose scan for comparison. Evaluation metrics were gamma pass rate (Γ) with 2 mm distance-to-agreement and 6% intensity criterion, voxel-wise Spearman correlation (ρ) and Jacobian ratio coefficient of variation (CoV JR ). Results: Comparing biomarkers derived from low (CTDI vol = 6.07 mGy) and high (CTDI vol = 60.7 mGy) dose 4DCT scans, mean Γ, ρ and CoV JR values were 93% ± 3%, 0.88 ± 0.03 and 0.04 ± 0.009, respectively. With IR applied, those values were 93% ± 4%, 0.90 ± 0.04 and 0.03 ± 0.003. Similarly, comparisons between BHCT-based biomarkers with variable dose (CTDI vol = 1.35-7.95 mGy) had mean Γ, ρ and CoV JR of 93% ± 4%, 0.97 ± 0.02 and 0.03 ± 0.006 without IR and 93% ± 4%, 0.97 ± 0.03 and 0.03 ± 0.007 with IR. Applying IR did not significantly change any metrics (p > 0.05). Discussion: This work demonstrated that CT-ventilation, calculated using the Jacobian determinant of an estimated transformation from a B-spline deformable image registration, is invariant to Hounsfield Unit (HU) variation caused by image noise. This advantageous finding may be leveraged clinically with potential applications including dose reduction and/or acquiring repeated low-dose acquisitions for improved ventilation characterization.

Robust quantification of CT-ventilation biomarker techniques and repeatability in a porcine model.

BACKGROUND: Biomarkers estimating local lung ventilation have been derived from computed tomography (CT) imaging using various image acquisition and post-processing techniques. CT-ventilation biomarkers have potential clinical use in functional avoidance radiation therapy (RT), in which RT treatment plans are optimized to reduce dose delivered to highly ventilated lung. Widespread clinical implementation of CT-ventilation biomarkers necessitates understanding of biomarker repeatability. Performing imaging within a highly controlled experimental design enables quantification of error associated with remaining variables. PURPOSE: To characterize CT-ventilation biomarker repeatability and dependence on image acquisition and post-processing methodology in anesthetized and mechanically ventilated pigs. METHODS: Five mechanically ventilated Wisconsin Miniature Swine (WMS) received multiple consecutive four-dimensional CT (4DCT) and maximum inhale and exhale breath-hold CT (BH-CT) scans on five dates to generate CT-ventilation biomarkers. Breathing maneuvers were controlled with an average tidal volume difference <200 cc. As surrogates for ventilation, multiple local expansion ratios (LERs) were calculated from the acquired CT scans using Jacobian-based post-processing techniques. L E R 2 $LER_2$ measured local expansion between an image pair using either inhale and exhale BH-CT images or two 4DCT breathing phase images. L E R N $LER_N$ measured the maximum local expansion across the 4DCT breathing phase images. Breathing maneuver consistency, intra- and interday biomarker repeatability, image acquisition and post-processing technique dependence were quantitatively analyzed. RESULTS: Biomarkers showed strong agreement with voxel-wise Spearman correlation ρ > 0.9 $\rho > 0.9$ for intraday repeatability and ρ > 0.8 $\rho > 0.8$ for all other comparisons, including between image acquisition techniques. Intra- and interday repeatability were significantly different (p < 0.01). LER2 and LERN post-processing did not significantly affect intraday repeatability. CONCLUSIONS: 4DCT and BH-CT ventilation biomarkers derived from consecutive scans show strong agreement in controlled experiments with nonhuman subjects.

Metrics of dose to highly ventilated lung are predictive of radiation-induced pneumonitis in lung cancer patients.

PURPOSE: To identify metrics of radiation dose delivered to highly ventilated lung that are predictive of radiation-induced pneumonitis. METHODS AND MATERIALS: A cohort of 90 patients with locally advanced non-small cell lung cancer treated with standard fractionated radiation therapy (RT) (60-66 Gy in 30-33 fractions) were evaluated. Regional lung ventilation was determined from pre-RT 4-dimensional computed tomography (4DCT) using the Jacobian determinant of a B-spline deformable image registration to estimate lung tissue expansion during respiration. Multiple voxel-wise population- and individual-based thresholds for defining high functioning lung were considered. Mean dose and volumes receiving dose ≥ 5-60 Gy were analyzed for both total lung-ITV (MLD,V5-V60) and highly ventilated functional lung-ITV (fMLD,fV5-fV60). The primary endpoint was symptomatic grade 2+ (G2+) pneumonitis. Receiver operator curve (ROC) analyses were used to identify predictors of pneumonitis. RESULTS: G2+ pneumonitis occurred in 22.2% of patients, with no differences between stage, smoking status, COPD, or chemo/immunotherapy use between G<2 and G2+ patients (P≥ 0.18). Highly ventilated lung was defined as voxels exceeding the population-wide median of 18% voxel-level expansion. All total and functional metrics were significantly different between patients with and without pneumonitis (P≤ 0.039). Optimal ROC points predicting pneumonitis from functional lung dose were fMLD ≤ 12.3 Gy, fV5 ≤ 54% and fV20 ≤ 19 %. Patients with fMLD ≤ 12.3 Gy had a 14% risk of developing G2+ pneumonitis whereas risk significantly increased to 35% for those with fMLD > 12.3 Gy (P = 0.035). CONCLUSIONS: Dose to highly ventilated lung is associated with symptomatic pneumonitis and treatment planning strategies should focus on limiting dose to functional regions. These findings provide important metrics to be used in functional lung avoidance RT planning and designing clinical trials.

Evaluating on-board kVCT- and MVCT-based dose calculation accuracy using a thorax phantom for helical tomotherapy treatments.

Purpose.To evaluate the impact of CT number calibration and imaging parameter selection on dose calculation accuracy relative to the CT planning process in thoracic treatments for on-board helical CT imaging systems used in helical tomotherapy.Methods and Materials.Direct CT number calibrations were performed with appropriate protocols for each imaging system using an electron density phantom. Large volume and SBRT treatment plans were simulated and optimized for planning CT scans of an anthropomorphic thorax phantom and transferred to registered kVCT and MVCT scans of the phantom as appropriate. Relevant DVH metrics and dose-difference maps were used to evaluate and compare dose calculation accuracy relative to the planning CT based on a variation in imaging parameters applied for the on-board systems.Results.For helical kVCT scans of the thorax phantom, median differences in DVH parameters for the large volume treatment plan were less than ±1% with dose to the target volume either over- or underestimated depending on the imaging parameters utilized for CT number calibration and thorax phantom acquisition. For the lung SBRT plan calculated on helical kVCT scans, median dose differences were up to -2.7% with a more noticeable dependence on parameter selection. For MVCT scans, median dose differences for the large volume plan were within +2% with dose to the target overestimated regardless of the imaging protocol.Conclusion.Accurate dose calculations (median errors of <±1%) using a thorax phantom simulating realistic patient geometry and scatter conditions can be achieved with images acquired with a helical kVCT system on a helical tomotherapy unit. This accuracy is considerably improved relative to that achieved with the MV-based approach. In a clinical setting, careful consideration should be made when selecting appropriate kVCT imaging parameters for this process as dose calculation accuracy was observed to vary with both parameter selection and treatment type.

Predicting pulmonary ventilation damage after radiation therapy for nonsmall cell lung cancer using a ResNet generative adversarial network.

BACKGROUND: Functional lung avoidance radiation therapy (RT) is a technique being investigated to preferentially avoid specific regions of the lung that are predicted to be more susceptible to radiation-induced damage. Reducing the dose delivered to high functioning regions may reduce the occurrence radiation-induced lung injuries (RILIs) and toxicities. However, in order to develop effective lung function-sparing plans, accurate predictions of post-RT ventilation change are needed to determine which regions of the lung should be spared. PURPOSE: To predict pulmonary ventilation change following RT for nonsmall cell lung cancer using machine learning. METHODS: A conditional generative adversarial network (cGAN) was developed with data from 82 human subjects enrolled in a randomized clinical trial approved by the institution's IRB to predict post-RT pulmonary ventilation change. The inputs to the network were the pre-RT pulmonary ventilation map and radiation dose distribution. The loss function was a combination of the binary cross-entropy loss and an asymmetrical structural similarity index measure (aSSIM) function designed to increase penalization of under-prediction of ventilation damage. Network performance was evaluated against a previously developed polynomial regression model using a paired sample t-test for comparison. Evaluation was performed using eight-fold cross-validation. RESULTS: From the eight-fold cross-validation, we found that relative to the polynomial model, the cGAN model significantly improved predicting regions of ventilation damage following radiotherapy based on true positive rate (TPR), 0.14±0.15 to 0.72±0.21, and Dice similarity coefficient (DSC), 0.19±0.16 to 0.46±0.14, but significantly declined in true negative rate, 0.97±0.05 to 0.62±0.21, and accuracy, 0.79±0.08 to 0.65±0.14. Additionally, the average true positive volume increased from 104±119 cc in the POLY model to 565±332 cc in the cGAN model, and the average false negative volume decreased from 654±361 cc in the POLY model to 193±163 cc in the cGAN model. CONCLUSIONS: The proposed cGAN model demonstrated significant improvement in TPR and DSC. The higher sensitivity of the cGAN model can improve the clinical utility of functional lung avoidance RT by identifying larger volumes of functional lung that can be spared and thus decrease the probability of the patient developing RILIs.

Considering Lumpectomy Cavity PTV Expansions: Characterization of Intrafraction Lumpectomy Cavity Motion.

PURPOSE: Accelerated partial breast irradiation and lumpectomy cavity boost radiation therapy plans generally use volumetric expansions from the lumpectomy cavity clinical target volume to the planning target volume (PTV) of 1 to 1.5 cm, substantially increasing the volume of irradiated breast tissue. The purpose of this study was to quantify intrafraction lumpectomy cavity motion during external beam radiation therapy to inform the indicated clinical target volume to PTV expansion. METHODS AND MATERIALS: Forty-four patients were treated with a whole breast irradiation using traditional linear accelerator-based radiation therapy followed by lumpectomy cavity boost using magnetic resonance (MR)-guided radiation therapy on a prospective registry study. Two-dimensional cine-MR images through the center of the surgical cavity were acquired during each boost treatment to define the treatment position of the lumpectomy cavity. This was compared with the reference position to quantify intrafraction cavity motion. Free-breathing technique was used during treatment. Clinical outcomes including toxicity, cosmesis, and rates of local control were additionally analyzed. RESULTS: The mean maximum displacement per fraction in the anterior-posterior (AP) direction was 1.4 mm. Per frame, AP motion was <5 mm in 92% of frames. The mean maximum displacement per fraction in the superior-inferior (SI) direction was 1.2 mm. Per frame, SI motion was <5 mm in 94% of frames. Composite motion was <5 mm in 89% of frames. Three-year local control was 97%. Eight women (18%) developed acute G2 radiation dermatitis. With a median follow-up of 32.4 months, cosmetic outcomes were excellent (22/44, 50%), good (19/44, 43%), and fair (2/44, 5%). CONCLUSIONS: In approximately 90% of analyzed frames, intrafraction displacement of the lumpectomy cavity was <5 mm, with even less motion expected with deep inspiratory breath hold. Our results suggest reduced PTV expansions of 5 mm would be sufficient to account for lumpectomy cavity position, which may accordingly reduce late toxicity and improve cosmetic outcomes.

CT-derived vessel segmentation for analysis of post-radiation therapy changes in vasculature and perfusion.

Vessel segmentation in the lung is an ongoing challenge. While many methods have been able to successfully identify vessels in normal, healthy, lungs, these methods struggle in the presence of abnormalities. Following radiotherapy, these methods tend to identify regions of radiographic change due to post-radiation therapytoxicities as vasculature falsely. By combining texture analysis and existing vasculature and masking techniques, we have developed a novel vasculature segmentation workflow that improves specificity in irradiated lung while preserving the sensitivity of detection in the rest of the lung. Furthermore, radiation dose has been shown to cause vascular injury as well as reduce pulmonary function post-RT. This work shows the improvements our novel vascular segmentation method provides relative to existing methods. Additionally, we use this workflow to show a dose dependent radiation-induced change in vasculature which is correlated with previously measured perfusion changes (R 2 = 0.72) in both directly irradiated and indirectly damaged regions of perfusion. These results present an opportunity to extend non-contrast CT-derived models of functional change following radiation therapy.

The Impact of Parameter Selection and Setup Conditions on Image Quality of an On-Board Helical Kilovoltage Computed Tomography System.

Purpose To evaluate the imaging performance of an on-board helical kilovoltage computed tomography (kVCT) system mounted on a helical tomotherapy unit for various imaging parameters and setup conditions. Methods Images of a commonly used computed tomography (CT) image quality phantom were acquired while varying the selection of available parameters (anatomy, mode, body size) as well as phantom positioning and size. Image quality metrics (IQM) including noise, uniformity, contrast, CT number constancy, and spatial resolution were compared for parameter and setup variations.  Results The use of fine mode improved noise and contrast metrics by 20-30% compared to normal mode and by nearly a factor of two compared to the coarse mode for otherwise identical protocols. Uniformity, CT number constancy, and spatial resolution were also improved for fine mode. Thorax and pelvis anatomy protocols improved noise, uniformity, and contrast metrics by 10-20% compared to images acquired with head protocols. No significant differences in CT number constancy or spatial resolution were observed regardless of anatomy choice. Increasing body size (milliampere second (mAs)/rotation) improved each image quality metric. Vertical and lateral phantom shifts of up to ±6 cm degraded noise and contrast metrics by up to 30% relative to the isocenter while also worsening uniformity and CT number constancy. IQM were also degraded substantially with the use of annuli to increase the phantom diameter (32 cm vs. 20 cm). Despite variations in image characteristics among the investigated changes, most metrics were within manufacturer specifications when applicable. Conclusion This work demonstrates the dependence of image quality on parameter selection and setup conditions for a helical kVCT system utilized in image-guided and adaptive helical tomotherapy treatments. While the overall image quality is robust to variations in imaging parameters, care should be taken when selecting parameters as patient size increases or positioning moves from the isocenter to ensure adequate image quality is still achieved.

Measuring Indirect Radiation-Induced Perfusion Change in Fed Vasculature Using Dynamic Contrast CT.

Recent functional lung imaging studies have presented evidence of an "indirect effect" on perfusion damage, where regions that are unirradiated or lowly irradiated but that are supplied by highly irradiated regions observe perfusion damage post-radiation therapy (RT). The purpose of this work was to investigate this effect using a contrast-enhanced dynamic CT protocol to measure perfusion change in five novel swine subjects. A cohort of five Wisconsin Miniature Swine (WMS) were given a research course of 60 Gy in five fractions delivered locally to a vessel in the lung using an Accuray Radixact tomotherapy system with Synchrony motion tracking to increase delivery accuracy. Imaging was performed prior to delivering RT and 3 months post-RT to yield a 28−36 frame image series showing contrast flowing in and out of the vasculature. Using MIM software, contours were placed in six vessels on each animal to yield a contrast flow curve for each vessel. The contours were placed as follows: one at the point of max dose, one low-irradiated (5−20 Gy) branching from the max dose vessel, one low-irradiated (5−20 Gy) not branching from the max dose vessel, one unirradiated (<5 Gy) branching from the max dose vessel, one unirradiated (<5 Gy) not branching from the max dose vessel, and one in the contralateral lung. Seven measurements (baseline-to-baseline time and difference, slope up and down, max rise and value, and area under the curve) were acquired for each vessel's contrast flow curve in each subject. Paired Student t-tests showed statistically significant (p < 0.05) reductions in the area under the curve in the max dose, and both fed contours indicating an overall reduction in contrast in these regions. Additionally, there were statistically significant reductions observed when comparing pre- and post-RT in slope up and down in the max dose, low-dose fed, and no-dose fed contours but not the low-dose not-fed, no-dose not-fed, or contralateral contours. These findings suggest an indirect damage effect where irradiation of the vasculature causes a reduction in perfusion in irradiated regions as well as regions fed by the irradiated vasculature.

Performance evaluation of image reconstruction algorithms for a megavoltage computed tomography system on a helical tomotherapy unit.

Objective. To evaluate the impact of image reconstruction algorithm selection, as well as imaging mode and the reconstruction interval, on image quality metrics for megavoltage computed tomography (MVCT) image acquisition for use in image-guided (IGRT) and adaptive radiotherapy (ART) on a next-generation helical tomotherapy system.Approach. A CT image quality phantom was scanned across all available acquisition modes for filtered back projection (FBP) and both iterative reconstruction (IR) algorithms available on the system. Image quality metrics including noise, uniformity, contrast, spatial resolution, and mean CT number were compared. Analysis of DICOM data was performed using ImageJ software and Python code. ANOVA single factor and Tukey's honestly significant difference post-hoc tests were utilized for statistical analysis.Main Results. Application of both IR algorithms noticeably improved noise and image contrast when compared to the FBP algorithm available on all previous-generation helical tomotherapy systems. Use of the FBP algorithm improved image uniformity and spatial resolution in the axial plane, though values for the IR algorithms were well within tolerances recommended for IGRT and/or MVCT-based ART implementation by the American Association of Physicists in Medicine (AAPM). Additionally, longitudinal resolution showed little dependence on the reconstruction algorithm, while a negligible variation in mean CT number was observed regardless of the reconstruction algorithm or acquisition parameters. Statistical analysis confirmed the significance of these results.Significance. An overall improvement in image quality for metrics most important to IGRT and ART-mainly image noise and contrast-was evident in the application of IR when compared to FBP. Furthermore, since other imaging parameters remain identical regardless of the reconstruction algorithm, this improved image quality does not come at the expense of additional patient dose or an increased scan acquisition time for otherwise identical parameters. These improvements are expected to enhance fidelity in IGRT and ART implementation.

Characterization of imaging performance of a novel helical kVCT for use in image-guided and adaptive radiotherapy.

ClearRT helical kVCT imaging for the Radixact helical tomotherapy system recently received FDA approval and is available for clinical use. The system is intended to enhance image fidelity in radiation therapy treatment planning and delivery compared to the prior MV-based onboard imaging approach. The purpose of this work was to characterize the imaging performance of this system and compare this performance with that of clinical systems used in image-guided and/or adaptive radiotherapy (ART) or computed tomography (CT) simulation, including Radixact MVCT, TomoTherapy MVCT, Varian TrueBeam kV OBI CBCT, and the Siemens SOMATOM Definition Edge kVCT. A CT image quality phantom was scanned across clinically relevant acquisition modes for each system to evaluate image quality metrics, including noise, uniformity, contrast, spatial resolution, and CT number linearity. Similar noise levels were observed for ClearRT and Siemens Edge, whereas noise for the other systems was ∼1.5-5 times higher. Uniformity was best for Siemens Edge, whereas most scans for ClearRT exhibited a slight "cupping" or "capping" artifact. The ClearRT and Siemens Edge performed best for contrast metrics, which included low-contrast visibility and contrast-to-noise ratio evaluations. Spatial resolution was best for TrueBeam and Siemens Edge, whereas the three kVCT systems exhibited similar CT number linearity. Overall, these results provide an initial indication that ClearRT image quality is adequate for image guidance in radiotherapy and sufficient for delineating anatomic structures, thus enabling its use for ART. ClearRT also showed significant improvement over MVCT, which was previously the only onboard imaging modality available on Radixact. Although the acquisition of these scans does come at the cost of additional patient dose, reported CTDI values indicate a similar or generally reduced machine output for ClearRT compared to the other systems while maintaining comparable or improved image quality overall.

Using 4D dose accumulation to calculate organ-at-risk dose deviations from motion-synchronized liver and lung tomotherapy treatments.

Tracking systems such as Radixact Synchrony change the planned delivery of radiation during treatment to follow the target. This is typically achieved without considering the location changes of organs at risk (OARs). The goal of this work was to develop a novel 4D dose accumulation framework to quantify OAR dose deviations due to the motion and tracked treatment. The framework obtains deformation information and the target motion pattern from a four-dimensional computed tomography dataset. The helical tomotherapy treatment plan is split into 10 plans and motion correction is applied separately to the jaw pattern and multi-leaf collimator (MLC) sinogram for each phase based on the location of the target in each phase. Deformable image registration (DIR) is calculated from each phase to the references phase using a commercial algorithm, and doses are accumulated according to the DIR. The effect of motion synchronization on OAR dose was analyzed for five lung and five liver subjects by comparing planned versus synchrony-accumulated dose. The motion was compensated by an average of 1.6 cm of jaw sway and by an average of 5.7% of leaf openings modified, indicating that most of the motion compensation was from jaw sway and not MLC changes. OAR dose deviations as large as 19 Gy were observed, and for all 10 cases, dose deviations greater than 7 Gy were observed. Target dose remained relatively constant (D95% within 3 Gy), confirming that motion-synchronization achieved the goal of maintaining target dose. Dose deviations provided by the framework can be leveraged during the treatment planning process by identifying cases where OAR doses may change significantly from their planned values with respect to the critical constraints. The framework is specific to synchronized helical tomotherapy treatments, but the OAR dose deviations apply to any real-time tracking technique that does not consider location changes of OARs.

Technical note: Tracking target/chest relationship changes during motion-synchronized tomotherapy treatments.

BACKGROUND: Radixact Synchrony® is an intrafraction motion tracking system for helical tomotherapy treatments that uses kV radiographs of the target and LEDs on the patient's chest to synchronize the movement of the radiation beam with the respiratory motion of the target. Several works have demonstrated Synchrony's ability to track target motion when the chest and target motions are perfectly correlated. PURPOSE: The purpose of this work was to determine Synchrony's ability to accurately adapt to scenarios with a changing target/chest correlation. METHODS: A custom ion chamber mimicking plug with embedded fiducials was placed inside a Delta4 Phantom+ and used as the tracking object. A separate motion stage was programmed to mimic chest motion. The target and chest surrogate phantom were programmed to move sinusoidally and two types of target/chest relationship changes were introduced: rigid shifts and linear drifts of the target position but not surrogate position. Tracking analysis was performed by comparing programmed phantom motion to log files of the Synchrony-modeled motion. No dosimetry was performed in this work. RESULTS: At the fastest imaging rate of 2 s/img, Synchrony accurately adapted for gradual drifts in the target location (up to 5 mm/min) with minor increases in tracking errors and adapted for an abrupt 5 mm shift after about 30 s (with an auto-pause threshold at 60 s). When the imaging period was longer (> 4 s/img), larger tracking errors (> 5 mm) were observed, and the treatment would be paused. The measured delta (MD) parameter (2D target localization error on the most recent image) was found to be a more responsive indicator of tracking errors than the potential difference (PD) parameter (3D estimator of tracking error based on all images in the model). Lastly, the effect of a recent update to the tracking algorithm was found to improve the ability of Synchrony to track target/chest relationship changes. CONCLUSIONS: This work demonstrated that Synchrony can adapt to gradual changes (drifts) in the target/chest relationship, but it takes a finite amount of time to adapt to abrupt shifts. Ability to adapt to these changes increases with increasing imaging frequency. Larger tracking errors were observed in this work than others have reported in the literature due to the introduction of target/chest correlation changes in this work. Future work needs to be performed investigating what type and magnitude of target/chest miscorrelations occur in patients. Lastly, users should ensure they are using the most recent software (3.0.1 or newer) to improve the ability of Synchrony to track these movements.

Radiation-induced airway changes and downstream ventilation decline in a swine model.

Purpose.To investigate indirect radiation-induced changes in airways as precursors to atelectasis post radiation therapy (RT).Methods.Three Wisconsin Miniature Swine (WMSTM) underwent a research course of 60 Gy in 5 fractions delivered to a targeted airway/vessel in the inferior left lung. The right lung received a max point dose <5 Gy. Airway segmentation was performed on the pre- and three months post-RT maximum inhale phase of the four-dimensional (4D) computed tomography (CT) scans. Changes in luminal area (Ai) and square root of wall area (WA) for each airway were investigated. Changes in ventilation were assessed using the Jacobian ratio and were measured in three different regions: the inferior left lung <5 Gy (ILL), the superior left lung <5 Gy (SLL), and the contralateral right lung <5 Gy (RL).Results.Airways (n = 25) in the right lung for all swine showed no significant changes (p = 0.48) in Ai post-RT compared to pre-RT. Airways (n = 28) in the left lung of all swine were found to have a significant decrease (p < 0.001) in Ai post-RT compared to pre-RT, correlated (Pearson R = -0.97) with airway dose. Additionally,WAdecreased significantly (p < 0.001) with airway dose. Lastly, the Jacobian ratio of the ILL (0.883) was lower than that of the SLL (0.932) and the RL (0.955).Conclusions.This work shows that for the swine analyzed, there were significant correlations between Ai andWAchange with radiation dose. Additionally, there was a decrease in lung function in the regions of the lung supplied by the irradiated airways compared to the regions supplied by unirradiated airways. These results support the hypothesis that airway dose should be considered during treatment planning in order to potentially preserve functional lung and reduce lung toxicities.

In Silico Single-Fraction Stereotactic Ablative Radiation Therapy for the Treatment of Thoracic and Abdominal Oligometastatic Disease With Online Adaptive Magnetic Resonance Guidance.

PURPOSE: Although SABR can improve oncologic outcomes for patients with oligometastatic disease, treatment of metastases near critical organs remains challenging. The purpose of this study is to determine the dosimetric feasibility of delivering magnetic resonance imaging (MRI)-guided adaptive SABR in a single fraction for abdominal and thoracic metastases. METHODS AND MATERIALS: Previously delivered MRI-guided radiation therapy plans for 20 patients with oligometastatic disease in the thorax or abdomen, with 70% (14/20) of the lesions within 8 mm from dose-limiting organs at risk (OARs), were used to simulate the delivery of 24 Gy in a single fraction. Planning objectives included planning target volume (PTV) V95% >90%, optimized PTV (PTVopt) V95% >90%, and PTVopt D99% >20 Gy with no OAR dose violations, where PTVopt removed overlap with nearby planning organ at risk volume (PRV). Single-fraction plans were simulated on the first 5 daily setup breath-hold MRI scans, and the plans were reoptimized to consider variations in setup position and anatomy. RESULTS: The mean PTV V95% for single-fraction SABR plans was lower compared with multifraction plans (mean 85.4% vs 92.6%, P = .02), but mean PTVopt V95% was not different (95.3% vs 98.2%, P = .62). After reoptimization of the single-fraction plan to the treatment day MRI, there was an increase in mean PTV V95% (85.0% vs 88.1%, P = .05), increase in mean PTVopt V95% (92.7% vs 96.3%, P = .02), increase in mean PTVopt D99% (19.7 Gy vs 23.8 Gy, P < .01), increase in mean frequency of meeting PTV D99% >20 Gy (52% vs 87%, P < .01), and increase in mean gross tumor volume minimum dose (17.5 Gy vs 19.3 Gy, P < .01). Reoptimization decreased mean frequency of OAR dose constraint violation (48% vs 0%, P < .01). CONCLUSIONS: Single-fraction MRI-guided SABR is a dosimetrically feasible treatment for oligometastases that allows for on-table adaptation to avoid OAR dose constraint violations, but this method requires clinical validation.